Growing evidence suggests that the immune system plays an important role in mediating resistance and susceptibility to gonococcal and chlamydial infection and disease. However, inherent flaws in most case- control studies of immune response to these agents limit the ability to understand the direction of causality. Additionally, much of the interaction between chlamydia and gonorrhea and their obligate human hosts occurs at the genital tract mucosa, yet mucosal immune responses to these organisms have been incompletely studied. Lastly, most researchers focus on the effects of immune defenses to the organism, neglecting the effects that the organisms might have on immune responses to other agents. Thus, the twin goals of the proposed research are to prospectively characterize the mucosal and systemic immune responses that mediate protection against or enhancement of susceptibility to gonococcal and chlamydial infection and disease; and to examine the mechanisms by which gonococcal and chlamydial infections alter mucosal immune responses to each other and to HIV. We hypothesize that the balance between antigen specific type I (interferon gamma) and type 2 (JL-4 and IL-10) immune responses determine resistance versus susceptibility to chlamydial and gonococcal infection and disease, and modify susceptibility to infection with other sexually transmitted agents. Two cohorts of commercial sex workers in Nairobi, Kenya will be followed for acquisition of gonococcal and chlamydial infections, and the occurrence of histologically confirmed PID. The relationship of incident and PID will be correlated with baseline measurements of antigen specific immune responses. The relationship of mucosal immune responses evoked by gonococcal and chlamydial infection on susceptibility to infection and disease due to other pathogens will be evaluated by characterizing the cytokine and humoral responses within the lower genital tract including the endometrium among individuals currently infected and 4 to 6 weeks post treatment. These studies will elucidate the specific immune responses that characterize resistance to gonococcal and chlamydial infection, and which correlate with the development of chlamydial and gonococcal PID.